A potential protein adjuvant derived from Mycobacterium tuberculosis Rv0652 enhances dendritic cells-based tumor immunotherapy

Seung Jun Lee, SungJae Shin, Moon Hee Lee, Min Goo Lee, Tae Heung Kang, Won Sun Park, Byoung Yul Soh, Jung Hee Park, Yong Kyoo Shin, Han Wool Kim, Cheol Heui Yun, In Duk Jung, Yeong Min Park

Research output: Contribution to journalArticle

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Abstract

A key factor in dendritic cell (DC)-based tumor immunotherapy is the identification of an immunoadjuvant capable of inducing DC maturation to enhance cellular immunity. The efficacy of a 50S ribosomal protein L7/L12 (rplL) from Mycobacterium tuberculosis Rv0652, as an immunoadjuvant for DC-based tumor immunotherapy, and its capacity for inducing DC maturation was investigated. In this study, we showed that Rv0652 is recognized by Toll-like receptor 4 (TLR4) to induce DC maturation, and pro-inflammatory cytokine production (TNF-alpha, IL-1beta, and IL-6) that is partially modulated by both MyD88 and TRIF signaling pathways. Rv0652-activated DCs could activate naïve T cells, effectively polarize CD4+ and CD8+ T cells to secrete IFN-gamma, and induce T cell-mediated-cytotoxicity. Immunization of mice with Rv0652-stimulated ovalbumin (OVA)-pulsed DCs resulted in induction of a potent OVA-specific CD8+ T cell response, slowed tumor growth, and promoted long-term survival in a murine OVA-expressing E.G7 thymoma model. These findings suggest that Rv0652 enhances the polarization of T effector cells toward a Th1 phenotype through DC maturation, and that Rv0652 may be an effective adjuvant for enhancing the therapeutic response to DC-based tumor immunotherapy.

Original languageEnglish
Article numbere104351
JournalPloS one
Volume9
Issue number8
DOIs
Publication statusPublished - 2014 Aug 7

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immunotherapy
Mycobacterium tuberculosis
dendritic cells
Immunotherapy
Dendritic Cells
adjuvants
Tumors
T-cells
neoplasms
ovalbumin
Ovalbumin
T-lymphocytes
Neoplasms
Proteins
proteins
T-Lymphocytes
Immunologic Adjuvants
thymoma
Immunization
Toll-Like Receptor 4

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Lee, Seung Jun ; Shin, SungJae ; Lee, Moon Hee ; Lee, Min Goo ; Kang, Tae Heung ; Park, Won Sun ; Soh, Byoung Yul ; Park, Jung Hee ; Shin, Yong Kyoo ; Kim, Han Wool ; Yun, Cheol Heui ; Jung, In Duk ; Park, Yeong Min. / A potential protein adjuvant derived from Mycobacterium tuberculosis Rv0652 enhances dendritic cells-based tumor immunotherapy. In: PloS one. 2014 ; Vol. 9, No. 8.
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abstract = "A key factor in dendritic cell (DC)-based tumor immunotherapy is the identification of an immunoadjuvant capable of inducing DC maturation to enhance cellular immunity. The efficacy of a 50S ribosomal protein L7/L12 (rplL) from Mycobacterium tuberculosis Rv0652, as an immunoadjuvant for DC-based tumor immunotherapy, and its capacity for inducing DC maturation was investigated. In this study, we showed that Rv0652 is recognized by Toll-like receptor 4 (TLR4) to induce DC maturation, and pro-inflammatory cytokine production (TNF-alpha, IL-1beta, and IL-6) that is partially modulated by both MyD88 and TRIF signaling pathways. Rv0652-activated DCs could activate na{\"i}ve T cells, effectively polarize CD4+ and CD8+ T cells to secrete IFN-gamma, and induce T cell-mediated-cytotoxicity. Immunization of mice with Rv0652-stimulated ovalbumin (OVA)-pulsed DCs resulted in induction of a potent OVA-specific CD8+ T cell response, slowed tumor growth, and promoted long-term survival in a murine OVA-expressing E.G7 thymoma model. These findings suggest that Rv0652 enhances the polarization of T effector cells toward a Th1 phenotype through DC maturation, and that Rv0652 may be an effective adjuvant for enhancing the therapeutic response to DC-based tumor immunotherapy.",
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Lee, SJ, Shin, S, Lee, MH, Lee, MG, Kang, TH, Park, WS, Soh, BY, Park, JH, Shin, YK, Kim, HW, Yun, CH, Jung, ID & Park, YM 2014, 'A potential protein adjuvant derived from Mycobacterium tuberculosis Rv0652 enhances dendritic cells-based tumor immunotherapy', PloS one, vol. 9, no. 8, e104351. https://doi.org/10.1371/journal.pone.0104351

A potential protein adjuvant derived from Mycobacterium tuberculosis Rv0652 enhances dendritic cells-based tumor immunotherapy. / Lee, Seung Jun; Shin, SungJae; Lee, Moon Hee; Lee, Min Goo; Kang, Tae Heung; Park, Won Sun; Soh, Byoung Yul; Park, Jung Hee; Shin, Yong Kyoo; Kim, Han Wool; Yun, Cheol Heui; Jung, In Duk; Park, Yeong Min.

In: PloS one, Vol. 9, No. 8, e104351, 07.08.2014.

Research output: Contribution to journalArticle

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AU - Lee, Seung Jun

AU - Shin, SungJae

AU - Lee, Moon Hee

AU - Lee, Min Goo

AU - Kang, Tae Heung

AU - Park, Won Sun

AU - Soh, Byoung Yul

AU - Park, Jung Hee

AU - Shin, Yong Kyoo

AU - Kim, Han Wool

AU - Yun, Cheol Heui

AU - Jung, In Duk

AU - Park, Yeong Min

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N2 - A key factor in dendritic cell (DC)-based tumor immunotherapy is the identification of an immunoadjuvant capable of inducing DC maturation to enhance cellular immunity. The efficacy of a 50S ribosomal protein L7/L12 (rplL) from Mycobacterium tuberculosis Rv0652, as an immunoadjuvant for DC-based tumor immunotherapy, and its capacity for inducing DC maturation was investigated. In this study, we showed that Rv0652 is recognized by Toll-like receptor 4 (TLR4) to induce DC maturation, and pro-inflammatory cytokine production (TNF-alpha, IL-1beta, and IL-6) that is partially modulated by both MyD88 and TRIF signaling pathways. Rv0652-activated DCs could activate naïve T cells, effectively polarize CD4+ and CD8+ T cells to secrete IFN-gamma, and induce T cell-mediated-cytotoxicity. Immunization of mice with Rv0652-stimulated ovalbumin (OVA)-pulsed DCs resulted in induction of a potent OVA-specific CD8+ T cell response, slowed tumor growth, and promoted long-term survival in a murine OVA-expressing E.G7 thymoma model. These findings suggest that Rv0652 enhances the polarization of T effector cells toward a Th1 phenotype through DC maturation, and that Rv0652 may be an effective adjuvant for enhancing the therapeutic response to DC-based tumor immunotherapy.

AB - A key factor in dendritic cell (DC)-based tumor immunotherapy is the identification of an immunoadjuvant capable of inducing DC maturation to enhance cellular immunity. The efficacy of a 50S ribosomal protein L7/L12 (rplL) from Mycobacterium tuberculosis Rv0652, as an immunoadjuvant for DC-based tumor immunotherapy, and its capacity for inducing DC maturation was investigated. In this study, we showed that Rv0652 is recognized by Toll-like receptor 4 (TLR4) to induce DC maturation, and pro-inflammatory cytokine production (TNF-alpha, IL-1beta, and IL-6) that is partially modulated by both MyD88 and TRIF signaling pathways. Rv0652-activated DCs could activate naïve T cells, effectively polarize CD4+ and CD8+ T cells to secrete IFN-gamma, and induce T cell-mediated-cytotoxicity. Immunization of mice with Rv0652-stimulated ovalbumin (OVA)-pulsed DCs resulted in induction of a potent OVA-specific CD8+ T cell response, slowed tumor growth, and promoted long-term survival in a murine OVA-expressing E.G7 thymoma model. These findings suggest that Rv0652 enhances the polarization of T effector cells toward a Th1 phenotype through DC maturation, and that Rv0652 may be an effective adjuvant for enhancing the therapeutic response to DC-based tumor immunotherapy.

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